GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells.
Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.
El, K; Gray, SM; Capozzi, ME; Knuth, ER; Jin, E; Svendsen, B; Clifford, A; Brown, JL; Encisco, SE; Chazotte, BM; Sloop, KW; Nunez, DJ; Merrins, MJ; D'Alessio, DA; Campbell, JE
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